STAT4 is required for the generation of Th1 and Th2, but not Th17 immune responses during monophosphoryl lipid A adjuvant activity

Sanjay Varikuti, Steve Oghumu, Gayathri Natarajan, Jennifer Kimble, Rachel H. Sperling, Ellen Moretti, Mark Kaplan, Abhay R. Satoskar

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

STAT4 is critical for the production of IFN-γ during the generation of Th1 immune responses. We investigated the role of STAT4 in mediating Th1-inducing activity of a vaccine adjuvant monophosphoryl lipid A (MPL-A) using the standard antigen ovalbumin (OVA) in STAT4KO mice. Our results show that splenocytes from STAT4KO mice displayed lower OVA-specific T-cell proliferation and IL-2 production compared with wild-type (WT) mice. Further, IFN-γ production was diminished in STAT4KO-derived splenocytes but the levels of IL-12 and TNF-α were similar compared with WT mice. Interestingly, STAT4 deficiency also led to a decrease in IL-10 and Th2 cytokines such as IL-4 and IL-13 upon MPL-A immunization, although IL-17 production was similar between WT- and STAT4KO-derived splenocytes. Our observations for defective Th1 and Th2 responses in STAT4KO mice were further supported by the low levels of Th1-associated IgG2a and Th2-associated IgG1 in the sera of these mice. Taken together, our results show that STAT4 plays a critical role in mediating both Th1 and Th2 responses upon immunization with MPL-A. Our study provides a better understanding of how MPL-A mediates T-cell activation which will be critical for future vaccine development.

Original languageEnglish (US)
Pages (from-to)565-570
Number of pages6
JournalInternational Immunology
Volume28
Issue number11
DOIs
StatePublished - Nov 1 2016

Fingerprint

Ovalbumin
Immunization
Vaccines
T-Lymphocytes
Interleukin-13
Interleukin-17
Interleukin-12
Interleukin-4
Interleukin-10
Interleukin-2
monophosphoryl lipid A
Immunoglobulin G
Cell Proliferation
Cytokines
Antigens
Serum

Keywords

  • IFN-γ
  • IL-2
  • IL-4
  • T cells
  • vaccine

ASJC Scopus subject areas

  • Immunology

Cite this

Varikuti, S., Oghumu, S., Natarajan, G., Kimble, J., Sperling, R. H., Moretti, E., ... Satoskar, A. R. (2016). STAT4 is required for the generation of Th1 and Th2, but not Th17 immune responses during monophosphoryl lipid A adjuvant activity. International Immunology, 28(11), 565-570. https://doi.org/10.1093/intimm/dxw038

STAT4 is required for the generation of Th1 and Th2, but not Th17 immune responses during monophosphoryl lipid A adjuvant activity. / Varikuti, Sanjay; Oghumu, Steve; Natarajan, Gayathri; Kimble, Jennifer; Sperling, Rachel H.; Moretti, Ellen; Kaplan, Mark; Satoskar, Abhay R.

In: International Immunology, Vol. 28, No. 11, 01.11.2016, p. 565-570.

Research output: Contribution to journalArticle

Varikuti, Sanjay ; Oghumu, Steve ; Natarajan, Gayathri ; Kimble, Jennifer ; Sperling, Rachel H. ; Moretti, Ellen ; Kaplan, Mark ; Satoskar, Abhay R. / STAT4 is required for the generation of Th1 and Th2, but not Th17 immune responses during monophosphoryl lipid A adjuvant activity. In: International Immunology. 2016 ; Vol. 28, No. 11. pp. 565-570.
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